Immune system recognition leads to immune responses

In this article, I briefly explain the occurrence of immune responses after recognition by the immune system.

Table of Contents

Immune system and its strategic program

There are innumerable cells of our immune system disseminated throughout our body. When our body is under attack from any foreign invader, the biggest task is to search for the precise cells to mount an immune response against the antigen. Our immune system applies several strategies to combat the situation.

Secretion of chemokines from infected tissues or nearby lymph nodes gives a signal to dendritic cells possessing the relevant chemokine receptors to exit from the bloodstream and enter the tissues.

When the dendritic cell gains entry into the tissues, it gets activated by binding of antigen to one of its innate immune receptors. Then, it migrates to the nearest lymph node and activates a T cell.

The migration of dendritic cells into the lymph node is eased by the upregulation of chemokine receptor CCR7 on the surface of dendritic cells. This facilitates their entry into the lymph node.

To slow the movement of blood flow and to facilitate leukocyte entry into the tissues, epithelial cells lining blood capillaries in affected areas change the expression of adhesion molecules on their cell surfaces.

Thus, the sequential events of chemokine receptor expression on dendritic cells and alteration of adhesion molecules in blood capillaries force the cells to leave the bloodstream and enter the tissues.

This facilitates the movement of antigen-presenting cells into the lymph node. Inside the lymph node, further alteration of the chemokine receptor molecule takes place due to the activation of T cells and B cells.

Strategy of activated macrophages and neutrophils to clear harmful pathogens

Activated macrophages and neutrophils eradicate pathogens without activating adaptive immunity. Through their innate immune receptors, macrophages and neutrophils recognize their proper ligands. Identification of the ligands and attaching to them make the cells active and ready to fight pathogens.

Both macrophages and neutrophils activate themselves, as a result of which their phagocytic activity is increased. As a result, they annihilate pathogens by digesting them in lysosomal vesicles.

Oxidative burst is another phenomenon where activated macrophages and neutrophils produce enormous harmful chemicals like hypochlorous acid, reactive nitrogen species, and peroxide and superoxide radicals. The phagocytosed microbes are killed by these toxic chemicals, present inside the phagolysosomes of macrophages and neutrophils.

On activation, both macrophages and neutrophils secrete cytokines like IL-1, IL-6, and TNF-α, which help to widen the blood vessels to increase blood flow, also known as vasodilation. Thus, more amount of cells and fluids move out of the blood vessels and enter into tissues.

Local mast cells secrete mediators like prostaglandins and histamines that sum with vasodilation and capillary leakage, which persuade fever.

All these events, including vasodilation, capillary leakage, cytokine secretion, and migration of cells into injured tissues, are four fundamental signs of inflammation, i.e., calor (heat), rubor (redness), tumor (swelling), and dolor (pain) respectively.

T cells and dendritic cells secrete cytokines that shows the path for subsequent immune response

Dendritic cells, through innate receptors, get antigen signaling and invoked to secrete cytokines. Different types of cytokines get secreted depending on the receptors and the environment of stimulation.

The type of cytokines secreted by dendritic cells is related to the type of T-cell response. It’s because the T cell is activated by the presentation of the antigen by the dendritic cell when the T cell bears receptors for its antigen.

A dendritic cell with a processed antigen is presented on its surface by an MHC-2 molecule, which is engaged with a naïve T_H cell in the lymph node. Then, it secretes IL-12 cytokines, which induce differentiation in the T helper cell or T_H1 cell. The T helper cell, in turn activates T_C cells (cytotoxic T cells) and macrophages and subsequently induces the B cells to secrete a certain type of antibodies.

Naïve B cells and T cells are short-lived but gain long-term survival upon antigen activation

Naïve T cells and B cells have a short lifespan in the circulation. However, when they come across an antigen-presenting cell with a processed antigen, they get an anti-apoptotic signal from the antigen. They stretch their life spans and can mediate their functions, i.e., cytokine and antibody secretion, respectively. Some of these activated T cells and B cells become memory cells and may gain lifelong survival.

An enzyme known as PI3 kinase (phosphatidyl inositol-3-kinase) gets activated after binding antigen. The enzyme’s activity is regulated when it binds to an adapter protein complex. The adapter protein complex is produced in response to antigen signaling.

Protein kinase Akt plays an important role in the phosphorylation and inactivation of the molecules responsible for apoptosis. It also increases the life span of antigen-activated lymphocytes. When the enzyme PI3 kinase binds to an adapter protein complex, it adds a phosphate group to a phospholipid inside its membrane. Thus, it activates the protein kinase Akt.

B cells and T cells start to divide and differentiate after antigen binding

When a naïve B cell comes in contact with an antigen, it starts to divide. Then, it is differentiated into antibody-secreting plasma cells and memory B cells. Some enzymes of the signal transduction pathways are specific only for activating B lymphocytes.

When T cells come in contact with antigens, initially for many days, they instruct their B cell partners to alter the genetic modifications in the antibody genes. This results in the generation of more efficient antibody molecules. Thus, these modifications result in the synthesis of different classes of antibodies.

When T cells come in contact with antigens, they start to differentiate and secrete different cytokines. These cytokines can direct various immune responses. When helper T cells start to differentiate, they initiate secreting cytokines. At the end of the differentiation process, they attain a higher capacity to secrete an array of cytokines.

The specific set of cytokines secreted by a differentiated T cell is dependent upon the binding antigen and the cytokines secreted by the antigen-presenting cell.

Different types of cytokines spur the secretion of several types of antibodies and promote macrophage activation and cytotoxic T-cell activity.

Conclusion

Our immune system applies many strategies to search for the precise cells to mount an immune response against a particular pathogen.

Macrophages and neutrophils recognize their proper ligands through their innate immune receptors. Through oxidative bursts, activated macrophages and neutrophils produce enormous harmful chemicals. These include hypochlorous acid, reactive nitrogen species, and peroxide and superoxide radicals.

Cytokines secreted by dendritic cells and T cells subsequently open the path for further immune response.